Norepinephrine and epinephrine responses to physiological and pharmacological stimulation in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by fatigue lasting 6 months or longer. CFS has been associated with a disturbed (re-)activity of the autonomic nervous system. However, the sympathetic adrenomedulla (SAM) remains under-examined in CFS.

To investigate SAM reactivity, we implemented a submaximal cycle ergometry (ERGO) and a pharmacological test (Insulin Tolerance Test, ITT) in 21 CFS patients and 20 age-, sex-, and BMI-matched controls. Plasma norepinephrine and epinephrine were collected once before and twice after the tests (+10/+20, and +30 min).

Lower baseline levels and attenuated responses of epinephrine to the ERGO were found in CFS patients compared to controls, while the groups did not differ in their responses to the ITT.

To conclude, we found evidence of altered sympathetic-neural and SAM reactivity in CFS. Exercise stress revealed a subtle catecholaminergic hyporeactivity in CFS patients. It is conceivable that inadequate catecholaminergic responses to physical exertion might contribute to CFS symptoms.

Copyright © 2013 Elsevier B.V. All rights reserved.

 

Source: Strahler J, Fischer S, Nater UM, Ehlert U, Gaab J. Norepinephrine and epinephrine responses to physiological and pharmacological stimulation in chronic fatigue syndrome. Biol Psychol. 2013 Sep;94(1):160-6. doi: 10.1016/j.biopsycho.2013.06.002. Epub 2013 Jun 13. https://www.ncbi.nlm.nih.gov/pubmed/23770415

 

Multiscale analysis of heart rate variability in non-stationary environments

Abstract:

Heart rate variability (HRV) is highly non-stationary, even if no perturbing influences can be identified during the recording of the data. The non-stationarity becomes more profound when HRV data are measured in intrinsically non-stationary environments, such as social stress. In general, HRV data measured in such situations are more difficult to analyze than those measured in constant environments.

In this paper, we analyze HRV data measured during a social stress test using two multiscale approaches, the adaptive fractal analysis (AFA) and scale-dependent Lyapunov exponent (SDLE), for the purpose of uncovering differences in HRV between chronic fatigue syndrome (CFS) patients and their matched-controls.

CFS is a debilitating, heterogeneous illness with no known biomarker. HRV has shown some promise recently as a non-invasive measure of subtle physiological disturbances and trauma that are otherwise difficult to assess. If the HRV in persons with CFS are significantly different from their healthy controls, then certain cardiac irregularities may constitute good candidate biomarkers for CFS.

Our multiscale analyses show that there are notable differences in HRV between CFS and their matched controls before a social stress test, but these differences seem to diminish during the test. These analyses illustrate that the two employed multiscale approaches could be useful for the analysis of HRV measured in various environments, both stationary and non-stationary.

 

Source: Gao J, Gurbaxani BM, Hu J, Heilman KJ, Emanuele Ii VA, Lewis GF, Davila M, Unger ER, Lin JM. Multiscale analysis of heart rate variability in non-stationary environments. Front Physiol. 2013 May 30;4:119. doi: 10.3389/fphys.2013.00119. ECollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667239/ (Full article)

 

Cognitive performance is of clinical importance, but is unrelated to pain severity in women with chronic fatigue syndrome

Abstract:

In various chronic pain populations, decreased cognitive performance is known to be related to pain severity. Yet, this relationship has not been investigated in patients with chronic fatigue syndrome (CFS). This study investigated the relationship between cognitive performance and (1) pain severity, (2) level of fatigue, and (3) self-reported symptoms and health status in women with CFS. Examining the latter relationships is important for clinical practice, since people with CFS are often suspected to exaggerate their symptoms.

A sample of 29 female CFS patients and 17 healthy controls aged 18 to 45 years filled out three questionnaires (Medical Outcomes Study 36-Item Short-Form Health Survey, Checklist Individual Strength (CIS), and CFS Symptom List) and performed three performance-based cognitive tests (psychomotor vigilance task, Stroop task, and operation span task), respectively.

In both groups, pain severity was not associated with cognitive performance. In CFS patients, the level of fatigue measured with the CFS Symptom List, but not with the CIS, was significantly correlated with sustained attention. Self-reported mental health was negatively correlated with all investigated cognitive domains in the CFS group. These results provide evidence for the clinical importance of objectively measured cognitive problems in female CFS patients.

Furthermore, a state-like measure (CFS Symptom List) appears to be superior over a trait-like measure (CIS) in representing cognitive fatigue in people with CFS. Finally, the lack of a significant relationship between cognitive performance and self-reported pain severity suggests that pain in CFS might be unique.

 

Source: Ickmans K, Meeus M, Kos D, Clarys P, Meersdom G, Lambrecht L, Pattyn N, Nijs J. Cognitive performance is of clinical importance, but is unrelated to pain severity in women with chronic fatigue syndrome. Clin Rheumatol. 2013 Oct;32(10):1475-85. doi: 10.1007/s10067-013-2308-1. Epub 2013 Jun 5. https://www.ncbi.nlm.nih.gov/pubmed/23737111

 

Use of an online survey to explore positive and negative outcomes of rehabilitation for people with CFS/ME

Abstract:

PURPOSE:First, to explore the experiences of people with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) of rehabilitation therapies so as to build an understanding of reasons for the discrepancy between the notably mixed experiences regarding effectiveness reported in patient surveys and the RCT evidence about the efficacy of Graded Exercise Therapy (GET). GET is a form of structured and supervised activity management that aims for gradual but progressive increases in physical activity. Second, to review patient experiences of two related rehabilitation approaches, Exercise on Prescription (EoP) and Graded Activity Therapy (GAT).

METHOD: An online survey conducted by the charity Action for ME generated qualitative data about 76 patient experiences of rehabilitation undertaken during or after 2008, examined using thematic analysis.

RESULTS: Both positive and negative experiences of rehabilitation were reported. Positive themes included supportive communication, the benefits of a routine linked with baseline setting and pacing, the value of goal setting, and increasing confidence associated with exercise. Negative themes included poor communication, feeling pushed to exercise beyond a sustainable level, having no setback plan, and patients feeling blamed for rehabilitation not working.

CONCLUSIONS: The negative themes may help explain the negative outcomes from rehabilitation reported by previous patient surveys. The negative themes indicate rehabilitation processes which contradict the NICE (National Institute for Health and Clinical Excellence) Guideline advice regarding GET, indicating that some clinical encounters were not implementing these. These findings suggest areas for improving therapist training, and for developing quality criteria for rehabilitation in CFS/ME.

Implications for Rehabilitation: The insensitive delivery of rehabilitation support for people with CFS/ME can explain negative outcomes reported in patient surveys. Therapist-patient collaboration, establishing a sustainable baseline and agreeing a setback plan are all examples of higher quality rehabilitation indicated by this research. Greater awareness of the positive and negative experiences of rehabilitation therapies should enable avoidance of the potential pitfalls identified in this research.

Positive experiences of rehabilitation therapies include supportive communication with a therapist, treatment which included routines and goals, and value attached to baselines and controlled pacing. By contrast, factors leading to negative experiences include poor communication and support, conflict in beliefs about CFS/ME and rehabilitation, pressure to comply with treatment, worsening of symptoms, baselines experienced as unsustainable, and feeling blamed for rehabilitation not working.

Comment in:

 

Source: Gladwell PW, Pheby D, Rodriguez T, Poland F. Use of an online survey to explore positive and negative outcomes of rehabilitation for people with CFS/ME. Disabil Rehabil. 2014;36(5):387-94. doi: 10.3109/09638288.2013.797508. Epub 2013 Jun 4. https://www.ncbi.nlm.nih.gov/pubmed/23735013

 

Adolescents and mothers value referral to a specialist service for chronic fatigue syndrome or myalgic encephalopathy (CFS/ME)

Abstract:

BACKGROUND: Paediatric chronic fatigue syndrome or myalgic encephalopathy (CFS/ME) is relatively common and disabling. Current guidance recommends referral to specialist services, although some general practitioners believe the label of CFS/ME is harmful and many are not confident about diagnosing CFS/ME. Aim Explore whether or not adolescents and their mothers value referral to a specialist service for young people with CFS/ME.

METHODS: A qualitative study nested within a feasibility study of interventions for CFS/ME [Specialist Medical Intervention and Lightning Evaluation (SMILE)]. In-depth interviews were undertaken with 13 mothers and 12 adolescents participating in the SMILE study. Transcripts were systematically assigned codes using the qualitative data organisation package NVivo and analysed thematically using techniques of constant comparison.

RESULTS: Gaining access to the specialist service was difficult and took a long time. Mothers felt that they needed to be proactive and persistent, partly because of a lack of knowledge in primary and secondary care. Having gained access, mothers felt the CFS/ME service was useful because it recognised and acknowledged their child’s condition and opened channels of dialogue between health-care professionals and education providers. Adolescents reported that specialist medical care resulted in better symptom management, although some adolescents did not like the fact that the treatment approach limited activity.

CONCLUSIONS: Adolescents and their mothers value receiving a diagnosis from a specialist service and making progress in managing CFS/ME. General practitioners should support adolescents with CFS/ME in accessing CFS/ME specialist services, consistent with current guidance.

 

Source: Beasant L, Mills N, Crawley E. Adolescents and mothers value referral to a specialist service for chronic fatigue syndrome or myalgic encephalopathy (CFS/ME). Prim Health Care Res Dev. 2014 Apr;15(2):134-42. doi: 10.1017/S1463423613000121. Epub 2013 Apr 25. https://www.ncbi.nlm.nih.gov/pubmed/23731646

 

Brain dysfunction as one cause of CFS symptoms including difficulty with attention and concentration

Abstract:

We have been able to reduce substantially patient pool heterogeneity by identifying phenotypic markers that allow the researcher to stratify chronic fatigue syndrome (CFS) patients into subgroups. To date, we have shown that stratifying based on the presence or absence of comorbid psychiatric diagnosis leads to a group with evidence of neurological dysfunction across a number of spheres.

We have also found that stratifying based on the presence or absence of comorbid fibromyalgia leads to information that would not have been found on analyzing the entire, unstratified patient group. Objective evidence of orthostatic intolerance (OI) may be another important variable for stratification and may define a group with episodic cerebral hypoxia leading to symptoms.

We hope that this review will encourage other researchers to collect data on discrete phenotypes in CFS to allow this work to continue more broadly. Finding subgroups of CFS suggests different underlying pathophysiological processes responsible for the symptoms seen. Understanding those processes is the first step toward developing discrete treatments for each.

 

Source: Natelson BH. Brain dysfunction as one cause of CFS symptoms including difficulty with attention and concentration. Front Physiol. 2013 May 20;4:109. doi: 10.3389/fphys.2013.00109. ECollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657628/ (Full article)

 

Neuromuscular strain as a contributor to cognitive and other symptoms in chronic fatigue syndrome: hypothesis and conceptual model

Abstract:

Individuals with chronic fatigue syndrome (CFS) have heightened sensitivity and increased symptoms following various physiologic challenges, such as orthostatic stress, physical exercise, and cognitive challenges. Similar heightened sensitivity to the same stressors in fibromyalgia (FM) has led investigators to propose that these findings reflect a state of central sensitivity.

A large body of evidence supports the concept of central sensitivity in FM. A more modest literature provides partial support for this model in CFS, particularly with regard to pain. Nonetheless, fatigue and cognitive dysfunction have not been explained by the central sensitivity data thus far.

Peripheral factors have attracted attention recently as contributors to central sensitivity. Work by Brieg, Sunderland, and others has emphasized the ability of the nervous system to undergo accommodative changes in length in response to the range of limb and trunk movements carried out during daily activity. If that ability to elongate is impaired-due to movement restrictions in tissues adjacent to nerves, or due to swelling or adhesions within the nerve itself-the result is an increase in mechanical tension within the nerve. This adverse neural tension, also termed neurodynamic dysfunction, is thought to contribute to pain and other symptoms through a variety of mechanisms. These include mechanical sensitization and altered nociceptive signaling, altered proprioception, adverse patterns of muscle recruitment and force of muscle contraction, reduced intra-neural blood flow, and release of inflammatory neuropeptides. Because it is not possible to differentiate completely between adverse neural tension and strain in muscles, fascia, and other soft tissues, we use the more general term “neuromuscular strain.”

In our clinical work, we have found that neuromuscular restrictions are common in CFS, and that many symptoms of CFS can be reproduced by selectively adding neuromuscular strain during the examination. In this paper we submit that neuromuscular strain is a previously unappreciated peripheral source of sensitizing input to the nervous system, and that it contributes to the pathogenesis of CFS symptoms, including cognitive dysfunction.

 

Source: Rowe PC, Fontaine KR, Violand RL. Neuromuscular strain as a contributor to cognitive and other symptoms in chronic fatigue syndrome: hypothesis and conceptual model. Front Physiol. 2013 May 16;4:115. doi: 10.3389/fphys.2013.00115. eCollection 2013.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655286/ (Full article)

 

Cognitive impairments associated with CFS and POTS

Abstract:

Chronic fatigue syndrome (CFS) is characterized by fatigue, sleep dysfunction, and cognitive deficits (Fukuda et al., 1994). Research surrounding cognitive functioning among patients with CFS has found difficulty with memory, attention, and information processing. A similar disorder, postural tachycardia syndrome (POTS), is characterized by increased heart rate, fatigue, and mental cloudiness (Raj et al., 2009). Potential implications of cognitive deficits for patients with CFS and/or POTS are discussed, including difficulties with school and/or employment.

A few biological theories (i.e., kindling, impairments in the central nervous system, and difficulty with blood flow) have emerged as potential explanations for the cognitive deficits reported in both CFS and POTS Future research should continue to examine possible explanations for cognitive impairments in CFS and POTS, and ultimately use this information to try and reduce cognitive impairments for these patients.

 

Source: Shanks L, Jason LA, Evans M, Brown A. Cognitive impairments associated with CFS and POTS. Front Physiol. 2013 May 16;4:113. doi: 10.3389/fphys.2013.00113. ECollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655280/ (Full article)

 

Diagnosis and management of chronic fatigue syndrome/myalgic encephalitis in black and minority ethnic people: a qualitative study

Abstract:

AIM: This study aims to explore the possible reasons for the lower levels of diagnosis of chronic fatigue syndrome/myalgic encephalitis (CFS/ME) in the black and minority ethnic (BME) population, and the implications for management.

BACKGROUND: Population studies suggest CFS/ME is more common in people from BME communities compared with the White British population. However, the diagnosis is made less frequently in BME groups.

METHODS: Semi-structured qualitative interviews were conducted with 35 key stakeholders in NW England. Interviews were analysed using open explorative thematic coding.

FINDINGS: There are barriers at every stage to the diagnosis and management of CFS/ME in people from BME groups. This begins with a lack of awareness of CFS/ME among BME respondents. Religious beliefs and the expectation of roles in the family and community mean that some people in BME groups may choose to manage their symptoms outside primary care using alternative therapies, prayer or spiritual healing. When accessing primary care, all participants recognised the possible influence of language barriers in reducing the likelihood of a diagnosis of CFS/ME. Stereotypical beliefs, including labels such as ‘lazy’ or ‘work shy’ were also believed to act as a barrier to diagnosis. Patients highlighted the importance of an on-going relationship with the general practitioner (GP), but perceived a high turnover of GPs in inner city practices, which undermined the holistic approach necessary to achieve a diagnosis.

CONCLUSION: Training is required for health professionals to challenge inaccurate assumptions about CFS/ME in BME groups. The focus on the individual in UK primary care may not be appropriate for this group due to the role played by the family and community in how symptoms can be presented and managed. Culturally sensitive, educational resources for patients are also needed to explain symptoms and legitimise consultation.

 

Source: Bayliss K, Riste L, Fisher L, Wearden A, Peters S, Lovell K, Chew-Graham C. Diagnosis and management of chronic fatigue syndrome/myalgic encephalitis in black and minority ethnic people: a qualitative study. Prim Health Care Res Dev. 2014 Apr;15(2):143-55. doi: 10.1017/S1463423613000145. Epub 2013 May 23. https://www.ncbi.nlm.nih.gov/pubmed/23702254

 

An open-label study of effects of acupuncture on chronic fatigue syndrome and idiopathic chronic fatigue: study protocol for a randomized controlled trial

Abstract:

BACKGROUND: Even though chronic fatigue syndrome and idiopathic chronic fatigue are quite common, there are no clearly known causes. Most treatments are therefore symptomatic in nature, and chronic fatigue syndrome and idiopathic chronic fatigue patients are highly interested in using oriental medicine or complementary and alternative medicine treatment. Acupuncture, one of the major treatments used in oriental medicine, is effective in treating various diseases. This study will attempt to analyze the effectiveness and safety of acupuncture in the treatment of chronic fatigue by comparing the two treatment groups (body acupuncture, Sa-am acupuncture) and the control group (usual care).

METHODS/DESIGN: This study consists of a four-center, three-arm, randomized, controlled, and open-label trial. One hundred and fifty participants are randomly divided into treatment groups A and B and a control group. The treatment groups will receive acupuncture treatments either two or three times per week for a total of 10 sessions over a period of 4 weeks. The control group will not receive acupuncture treatments and will continue their usual care during this period. The primary outcome variable is the Fatigue Severity Scale, which will be utilized 5 weeks after randomization. Secondary outcome variables are the Fatigue Severity Scale at 13 weeks, a short form of the Stress Response Inventory, the Beck Depression Inventory, the Numeric Rating Scale, and the EuroQol-5 Dimension at 5 and 13 weeks after randomization.

DISCUSSION: This study will provide evidence with high external validity on the effectiveness and safety of acupuncture as a treatment for chronic fatigue syndrome and idiopathic chronic fatigue.

TRIAL REGISTRATION: Clinical Research Information Service KCT0000508.

 

Source: Kim JE, Hong KE, Kim HJ, Choi JB, Baek YH, Seo BK, Lee S, Kang KW, Lee MH, Kim JH, Lee S, Jung SY, Jung HJ, Shin MS, Choi SM. An open-label study of effects of acupuncture on chronic fatigue syndrome and idiopathic chronic fatigue: study protocol for a randomized controlled trial. Trials. 2013 May 21;14:147. doi: 10.1186/1745-6215-14-147. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663812/ (Full article)